We have demonstrated that alpha-haloacetophenone oximes can function as selective reagents for the alkylation of the active sites of enzymes like papain. We are presently extending our research to other enzyme systems and also probing the specificity of new alpha-haloalkyl ketoximes we have prepared as potential active site alkylating agents. The new compounds include the syn- and anti-isomers of the oxime of N-toluenesulfonyl phenylalanyl chloromethyl ketone, an alpha-halo ketone which is a well known enzyme inactivator. In view of the suggestion that the mode of action of tumor inhibitors like taxodone and vernolepin may involve the selective alkylation of certain protein sulfhydryl groups, we have sent and plan to continue to send NCI those alpha-haloalkyl oximes which show marked selectivity in the alkylation of sulfhydryl groups in enzymes. Additionally, we have been pursuing very actively the application of the chemistry of ketoximes in facilitating peptide synthesis by the solid phase method. Using polymer-bound ketoxime esters we have prepared protected peptide fragments. These fragments are removed from the polymer with a mild hydrazine treatment, and then after purification and activation they are coupled in solution.